Adipocytokine dysregulation, abnormal glucose metabolism, and lipodystrophy in HIV-infected adolescents receiving protease inhibitors.

BACKGROUND: Lipodystrophy is common in HIV-infected patients receiving protease inhibitors (PIs), stavudine, and zidovudine. Adipocytokines may be altered in lipodystrophy. We evaluated risk factors, adipocytokine levels, insulin resistance, and lipid profiles in HIV-infected adolescents with different lipodystrophy types. METHODS: A cross-sectional study was conducted in 80 perinatally HIV-infected adolescents receiving PI-based highly active antiretroviral therapy for ≥ 6 months. Patients underwent oral glucose tolerance tests and measurements of high-molecular-weight (HMW) adiponectin, leptin, resistin, insulin, and lipids. They were classified into 3 groups based on the clinical findings: no lipodystrophy, isolated lipoatrophy, and any lipohypertrophy (isolated lipohypertrophy or combined type). RESULTS: Of the 80 patients (median age, 16.7 years), 18 (22.5%) had isolated lipoatrophy, while 8 (10%) had any lipohypertrophy (four with isolated lipohypertrophy, and four with the combined type). In a multivariate analysis, longer exposure to stavudine (OR: 1.03; 95% CI, 1.01-1.06; p = 0.005) and indinavir (OR: 1.03; 95% CI, 1.01-1.06; p = 0.012) were associated with lipoatrophy, while longer exposure to didanosine (OR: 1.04; 95% CI, 1.01-1.08; p = 0.017) and indinavir (OR: 1.10; 95% CI, 1.00-1.21; p = 0.045) were associated with any lipohypertrophy. Leptin levels were highest in the any-lipohypertrophy group and lowest in the isolated-lipoatrophy group (p = 0.013). HMW adiponectin levels were significantly lowest in the any-lipohypertrophy group and highest in the no-lipodystrophy group (p = 0.001). There were no significant differences in the levels of resistin among the three groups (p = 0.234). The prevalence of insulin resistance (p = 0.002) and prediabetes/diabetes (p < 0.001) were significantly highest in the any-lipohypertrophy group. Patients with lipoatrophy and those without lipodystrophy had comparable degrees of insulin resistance (p = 0.292). In multiple linear regression analysis, adjusted for age, sex, and waist-height ratio, HMW adiponectin levels were associated with Matsuda index (ß = 0.5; p = 0.003) and quantitative insulin sensitivity check index (QUICKI) (ß = 40.1; p = 0.010) and almost significantly associated with homeostatic model assessment of insulin resistance (HOMA-IR) (p = 0.054). Leptin and resistin levels were not associated with HOMA-IR, Matsuda index, or QUICKI (all p > 0.05). CONCLUSIONS: Abnormal glucose metabolism and dysregulation of adipocytokines were common in the HIV-infected adolescents with lipohypertrophy and the combined type. Preventive screening for cardiovascular diseases caused by metabolic alterations should be routinely performed.

Time to Serological Cure and Associated Factors Among Syphilis Patients With and Without HIV in a Sexually Transmitted Infections Center, Thailand.

BACKGROUND: Together with clinical correlation, nontreponemal titers are used to monitor treatment outcomes. Syphilis patients with HIV and without HIV coinfection were found to have different serological responses after treatment. This study aims to determine time to serological cure for treatment of syphilis and factors associated with it in patients with and without HIV. METHOD: A descriptive study of syphilis patients who visited Bangrak STIs Center between January 1, 2007, and December 31, 2016. Univariate analysis was done to determine factors associated with serological outcomes. Survival curve analysis and multivariate Cox regression analysis were applied to compare time to serological cure between patients with various characteristics. RESULTS: Of 497 syphilis patients, 62.1% had serological cure, 2.2% had nonresponse, 4.6% had treatment failure or reinfection, 9.9% had serofast status, and 21.2% were undetermined because of loss to follow-up. The time to serological cure was 110 days (95% confidence interval [CI], 59-163 days) and 102 days (95% CI, 94-110 days) among patients with HIV and without HIV, respectively (P = 0.162). Time to serological cure was significantly faster in early syphilis and baseline titer ≥1:32. After adjustment with the Cox regression model, patients with early syphilis were associated with serological cure with a hazard ratio of 1.75 (95% CI, 1.32-2.32). Time to serological cure among early syphilis patients was significantly longer in HIV-positive than HIV-negative patients (P = 0.002), whereas no difference was observed in late syphilis (P = 0.104). CONCLUSION: Early syphilis was associated with faster time to serological cure. HIV patients with early syphilis took longer time to reach serological cure than did HIV-negative patients, whereas no such a difference was observed in late syphilis.

PARTNER NOTIFICATION OUTCOMES AMONG MALE GONORRHEA PATIENTS AT BANGRAK HOSPITAL, BANGKOK, THAILAND.

Partner notification (PN) is an important strategy to control sexually transmitted infections. The objective of this study was to assess the outcomes of PN in order to improve control of sexually transmitted infections. We retrospectively reviewed heterosexual male gonorrhea cases who presented for treatment to Bangrak Hospital during 2008 to determine the percent PN, the percent of successful partner management (SPM) and the factors associated with both. We used univariate and multivariate analyses to determine significant associations between characteristics of index cases and PN outcomes. We reviewed the medical records of 418 index cases. The median age of the subjects reviewed was 30 years old (range: 14-63). Six hundred ninety-two partners were identified. Of those, 367 partners (53.0%) were notified by 311 index cases; 95 partners (25.9% of the notifications) of the 89 index cases presented for treatment. The medical records of 92 partners were available to review: 61 (66%) had gonorrhea, chlamydia, or genital herpes infections. The median period from being notified to seeking care was 2.5 days (range: 0-92); 80% sought care within 9 days of notification. Spouses and girlfriends were the major partners being notified and had greater SPM. On multivariate analysis, a greater notification rate was found among index cases who were government workers or had a steady relationship. A higher SPM rate was associated with index cases who were aged ≥25 years, married or had a steady relationship. The PN rate among the studied index cases was inadequate. Further studies are needed to develop successful methods to improve PN rates and SPM rates in order to improve sexually transmitted infection control in the study population.

Low density lipoprotein receptor-related protein 5 gene polymorphisms and osteoporosis in Thai menopausal women.

BACKGROUND: Osteoporosis, characterized by low bone mineral density (BMD) and high bone fracture risk, is prevalent in Thai menopausal women. Genetic factors are known to play a key role in BMD. Low density lipoprotein receptor-related protein 5 (LRP5), a co-receptor in the Wnt/beta-catenin pathway, is involved in many aspects of bone biology. As coding single nucleotide polymorphisms (cSNPs) of LRP5, including A1330V (rs3736228), and Asian-related Q89R (rs41494349) and N740N (rs2306862), are associated with lowered BMD, this study aimed to determine the relationship between these LRP5 polymorphisms and BMD in 277 Thai menopausal women. RESULTS: Only rs3736228 deviated from the Hardy-Weinberg equilibrium of allele frequency (p = 0.022). The median, range and p value for the BMD related to each SNP parameter were compared (Mann-Whitney U test). Significant differences were observed between wild-type and risk alleles for both rs3736228 (total radial, p = 0.011; and radial 33, p = 0.001) and rs2306862 (radial 33: p = 0.015) SNPs, with no significant difference for rs41494349 SNP. Linkage disequilibrium was strong for both rs3736228 and rs2306862 SNPs. Haplotype analysis identified high CC frequency in both normal and osteopenia/osteoporosis groups, with a significant odds ratio for carrying the TT haplotype; however, this was non-significant after adjusting for age. Multivariate binary logistic regression analysis performed for rs3736228 showed that individuals with a body mass index <25 kg/m(2) had an increased risk of osteoporosis for each decade, but the polymorphism had no effect. CONCLUSIONS: This study did not identify LRP5 polymorphisms as a risk factor for osteoporosis in Thai menopausal women. Further studies with larger sample sizes are needed to further clarify the role of LRP5 as a genetic determinant of osteoporosis.

ADIPOQ POLYMORPHISMS AMONG THAIS WITH PRE-DIABETES.

Studies have shown that polymorphisms of adiponectin gene (ADIPOQ) are associated with risk of developing type 2 diabetes mellitus (T2DM). However, no studies have investigated the association between genetic variants of ADIPOQ and pre-diabetes, a group at higher risk for developing T2DM. A total of 75 pre-diabetes and 130 normal subjects were recruited from volunteers in Bangkok, Thailand. Individuals with pre-diabetes were selected based on American Diabetes Association diagnostic criteria. Six ADIPOQ polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism technique. ADIPOQ polymorphism rs266729 C>G is significantly associated with pre-diabetes (p = 0.006). CG/GG genotypes were found among 60% and 40% of pre-diabetes and normal subjects, respectively. SNP rs266729 C>G was associated with increased pre-diabetes risk (OR = 2.64; 95% CI: 1.18-5.89, p = 0.018). No significant differences were found between pre-diabetes and normal subjects for other ADIPOQ polymorphisms. However, haplotype analysis revealed that haplotype GGTAAT is significantly associated with pre-diabetes when compared with GCGAAC reference haplotype (OR = 22.31; 95% CI: 1.37-361.93, p = 0.03). Our data indicate that ADIPOQ rs266729 C>G polymorphism may contribute to the genetic risk of pre-diabetes and provide preliminary data useful in genetic screening for pre-diabetes among Thais.

Homocysteine but not serum amyloid A, vitamin A and E related to increased risk of metabolic syndrome in post-menopausal Thai women.

This study aims to investigate serum amyloid A, homocysteine, and biochemical-anthropometric measurements in post-menopausal women with and without metabolic syndrome (MS), and determine whether serum amyloid A and homocysteine are linked to MS among this group. This study was performed with 405 post-menopausal Thai volunteers with a mean age of 57.95±5.90 years (135 subjects with MS and 270 subjects without MS). The levels of serum amyloid A, homocysteine, vitamins, glucose, and lipids were measured. Homocysteine levels were significantly higher in the group with MS than in that without MS (p<0.001), whereas for serum amyloid A, vitamin A, vitamin E and vitamin B12, there were no significant differences. There were significant differences between the groups in folate, HDL-C, and anthropometric measurements (p<0.001). Thirty seven percent of the group with MS and 14.1% of the group without MS were classified as having hyperhomocysteinemia (p<0.001). Furthermore, logistic regression analysis revealed that hyperhomocysteinemia (odds ratio (OR): 2.67, 95% confidence interval (95%CI): 1.57-4.58), low folate (OR: 1.79, 95%CI: 1.11-2.89), and BMI (OR: 1.25, 95%CI: 1.16-1.33) were significantly related to MS. These findings suggest that increased homocysteine levels and decreased folate concentrations may influence susceptibility to MS and this effect may be an early event in the development of cardiovascular diseases among post-menopausal women. Therefore, there is a need to evaluate homocysteine levels, especially among post-menopausal Thai women.

Effects of PCSK1 genetic variants on obesity among Thai children and their family members: in relation to health risk, and biochemical and anthropometric parameters.

Single nucleotide polymorphisms (SNPs) in PCSK1, namely, rs6234, rs6235, and rs271939 have been linked to obesity in European population; and rs3811951 has also been connected to type 2 diabetes and obesity parameters in Chinese population. In this family-based case-control study, we analyzed links between PCSK1 genetic variants and obesity in Thai children and their families. Eleven obese children with a percent weight for height > or = 140 who had family history of obesity and 69 family members were recruited. SNPs rs6234, rs6235, rs3811951, and rs271939 of PCSK1 were analyzed using PCR and gene sequencing methods. DNA of 200 normal weight subjects was used as control. Participants with variant genotypes in the rs6234-6235 pair are at significantly more risk of being obese [OR = 2.44 (1.35-4.43), p = 0.003], and also at increased risk of being severely obese (obese class III) [OR = 3.03 (1.20-7.66), p = 0.015]. Variant rs3811951 showed no association with being obese, but is significantly linked to an increased risk of being severely obese [OR = 3.59 (1.42-9.08) p = 0.005]. Moreover, high density lipoprotein (HDL)-C levels between normal and variant rs3811951 group differed considerably, with patients with variant genotype having a lower HDL-C level (p = 0.037). Thus, Thais carrying SNPs rs6234-5 are at increased risk of being obese, and the risk of severe obesity increases when carrying both rs6234-5 and rs3811951, but not with rs271939. Furthermore, patients with genetic variations at rs3811951 are at risk of having low HDL-C levels.

Medical and economic burden of chronic hepatitis B patients at Queen Savang Vadhana Memorial Hospital.

OBJECTIVE: To study and to compare the medical and economic burden among chronic hepatitis B (CHB) patients. MATERIAL AND METHOD: A prospective observational study was conducted among 129 adult CHB patients. The medical burden was assessed by using the EuroQol-5D (EQ-5D) and the Chronic Liver Disease Questionnaire (CLDQ) at initial day, the six and 12-month follow-up. The economic burden was assessed in term of total cost per case per year RESULTS: At one-year follow-up, the mean age of 129 patients was 41.6 (SD = 11.8) years. For medical burden at over time, CHB with antiviral drugs (ARV) for hepatitis B infection had a significant decreased in percentage of anxiety, and increased the mean (SD) CLDQ score. The mean total costs per case per year of CHB without ARV (52 cases), CHB with antiviral drugs (50 cases), and CHB with cirrhosis/hepatocellular carcinoma (HCC) with ARV (27 cases) were significantly different (p < 0.001) with USD 615.9 (SD = 688.0), 1,777.4 (SD = 1,220.4), and 2,651.3 (SD = 3,885.0), respectively. CONCLUSION: CHB causes a great economic burden in Thailand Early antiviral drugs treatment prevents complication in CHB patients.

Association of MTHFR C677T polymorphism with bone mineral density of osteoporosis in postmenopausal Thai women.

BACKGROUND: Osteoporosis and osteopenia is rising with the increase in numbers of postmenopausal women. Methylenetetrahydrofolate reductase (MTHFR), a homocysteine catabolizing enzyme, is involved in the regulation of bone mineral density (BMD). The association between MTHFR C677T polymorphism with osteoporosis in postmenopausal Thai women is hitherto unclear. OBJECTIVE: To investigate the association between MTHFR C677T and BMD in postmenopausal Thai women. MATERIAL AND METHOD: The study subjects consisted of 346 postmenopausal Thai women volunteers. Standard dual-energy X-ray absorptiometry (DXA) was used for measurement of BMD T-score. Restriction fragment length polymorphism (RFLP) analysis was used for measurement of MTHFR C677T polymorphism. RESULTS: In the evaluation of 346 postmenopausal Thai women heterozygous (CT) genotype had a risk of osteopenia than normal control (odds ratio (OR) = 5.66, p < 0.001). BMD T-scores at each bone position revealed that heterozygous (CT) genotype had increased risk of osteopenic bones than normal controls at lumbar spines 1, 2, and 4 (OR = 2.48, p < 0.001, OR = 1.98, p = 0.008 and OR = 1.83, p = 0.016 respectively), ward's triangle (OR = 2.08, p = 0.008), and head of radius (OR = 2.95, p = 0.008). CONCLUSION: These results indicate the possibility of using MTHFR C677T polymorphism to identify postmenopausal Thai women at high risk of osteopenia.

Long term outcomes of nevirapine containing antiretroviral therapy at a center in Thailand.

This retrospective cohort study was conducted at Chon Buri Hospital, Thailand, to determine the long term outcomes of patients taking Nevirapine (NVP) containing antiretroviral therapy (ART). Patients taken NVP at least 5 years were included. Two hundred eighty-five patients met inclusion criteria and were included in the study. The median age of patients was 35 years; the median baseline CD4 was 66 cells/mm3 and the median follow-up was 7 years. Ninety-two point four percent and 90.2% of patients achieved virological success at year 5 and year 7, respectively. The median rise in CD4 count from baseline to year 5 was 354 cells/mm3 (IQR 235.5-487 cells/mm3) and at year 7 was 387 cells/mm3 (IQR 272-557 cells/mm3). Thirty-eight point eight percent of patients had a CD4 count > or = 500 cells/mm3 at year 5 and 41.6% at year 7. Rash/hypersensitivity occurred in 2 patients after 5 years and was transient. Elevated liver enzymes occurred in 5 patients after 5 years. NVP-containing ART yielded high virological-success rates. Long-term immunological response, safety and durability were also high.

Treatment-Seeking Behaviors and Knowledge, Attitude and Practices among Suspected Dengue Adult Patients at the Hospital for Tropical Diseases, Bangkok, Thailand.

Dengue infection is a major public health problem in Thailand with an increasing incidence in the adult population. Patients' knowledge, attitude and practices (KAP) with regarding dengue infection have direct influences on treatment-seeking behaviors and clinical outcomes. We conducted a cross-sectional study to assess the KAP and treatment-seeking behaviors of suspected dengue adult patients attending the Hospital for Tropical Diseases (HTD) in Bangkok, from March 2014 to February 2015. Among 167 participants, the majority of participants (87.9%) were unaware of dengue infection and most of them reported initial self-medication (95.2%). The mean days of fever before attending to the HTD was 4.9 ± 1.7 days. Outpatient cases reported seeking care significantly earlier than inpatient cases (mean: 3.1 days vs. 5.0 days; p < 0.001). The majority of patients believed that dengue infection has a high mortality rate (63%) and must be treated in hospital (91.3%), highlighting the lack of understanding and misperceptions regarding dengue-related knowledge in the general population. Patients who reported recent or current dengue infection in their family or neighborhood sought medical care early and reported good preventive practices. Health education should focus on the adult population to improve awareness of dengue symptoms and promote early treatment-seeking behavior.

Safety and immunogenicity of an inactivated recombinant Newcastle disease virus vaccine expressing SARS-CoV-2 spike: Interim results of a randomised, placebo-controlled, phase 1 trial.

Background: Production of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and middle-income countries is needed. NDV-HXP-S is an inactivated egg-based recombinant Newcastle disease virus vaccine expressing the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It's being developed by public sector manufacturers in Thailand, Vietnam, and Brazil; herein are initial results from Thailand. Methods: This phase 1 stage of a randomised, dose-escalation, observer-blind, placebo-controlled, phase 1/2 trial was conducted at the Vaccine Trial Centre, Mahidol University (Bangkok). Healthy males and non-pregnant females, aged 18-59 years and negative for SARS-CoV-2 antibodies, were eligible. Participants were randomised to receive one of six treatments by intramuscular injection twice, 28 days apart: 1 µg, 1 µg+CpG1018 (a toll-like receptor 9 agonist), 3 µg, 3 µg+CpG1018, 10 µg, or placebo. Participants and personnel assessing outcomes were masked to treatment. The primary outcomes were solicited and spontaneously reported adverse events (AEs) during 7 and 28 days after each vaccination, respectively. Secondary outcomes were immunogenicity measures (anti-S IgG and pseudotyped virus neutralisation). An interim analysis assessed safety at day 57 in treatment-exposed individuals and immunogenicity through day 43 per protocol. ClinicalTrials.gov (NCT04764422). Findings: Between March 20 and April 23, 2021, 377 individuals were screened and 210 were enroled (35 per group); all received dose one; five missed dose two. The most common solicited AEs among vaccinees, all predominantly mild, were injection site pain (<63%), fatigue (<35%), headache (<32%), and myalgia (<32%). The proportion reporting a vaccine-related AE ranged from 5·7% to 17·1% among vaccine groups and was 2·9% in controls; there was no vaccine-related serious adverse event. The 10 µg formulation's immunogenicity ranked best, followed by 3 µg+CpG1018, 3 µg, 1 µg+CpG1018, and 1 µg formulations. On day 43, the geometric mean concentrations of 50% neutralising antibody ranged from 122·23 international units per mL (IU/mL; 1 µg, 95% confidence interval (CI) 86·40-172·91) to 474·35 IU/mL (10 µg, 95% CI 320·90-701·19), with 93·9% to 100% of vaccine groups attaining a ≥ 4-fold increase over baseline. Interpretation: NDV-HXP-S had an acceptable safety profile and potent immunogenicity. The 3 µg and 3 µg+CpG1018 formulations advanced to phase 2. Funding: National Vaccine Institute (Thailand), National Research Council (Thailand), Bill & Melinda Gates Foundation, National Institutes of Health (USA).

Decreased retinol transport proteins in Thai post-menopausal women with osteoporosis.

High vitamin A ingestion or high serum retinol have been postulated to increase the risk of fractures and osteoporosis by reduced bone mineral density (BMD). Retinol is carried and transported to the tissues bound to retinol binding protein 4 (RBP4) and transthyretin (TTR). The relationships between retinol, retinol transport protein, retinol binding protein 4 (RBP4) and transthyretin (TTR) and BMD and osteoporosis are unclear. To examine the association between retinol and RBP4 and TTR and osteoporosis, 73 osteoporotic and 71 normal Thai postmenopausal women were studied. RBP4 and retinol levels did not differ between the groups. Serum TTR was significantly higher in control than osteoporotic subjects (89.47 and 144.53 microg/ml, respectively, p = 0.003, Mann-Whitney U test). TTR was positively correlated with BMD at several sites, such as the total radius bone (r = 0.172, p = 0.008, Spearman rank test). Osteoporosis risk was analyzed with binary logistic regression. Lean elderly Thais with lower TTR levels had a higher risk of osteoporosis. RBP4 and retinol levels had no relationship with disease status among Thai post-menopausal women. These results suggest calcium, minerals, vitamins and the retinol transport protein, transthyretin may be involved in the pathogenesis of osteoporosis.

Lung Ultrasound Findings of Patients with Dengue Infection: A Prospective Observational Study.

Lung ultrasound (LUS) is a more sensitive method of detecting pathological pulmonary changes than chest X-ray. Therefore, LUS for patients with dengue could be an important tool for the early detection of pleural effusions and pulmonary edema signifying capillary plasma leakage, which is the hallmark of severe dengue pathophysiology. We conducted a prospective observational study of pulmonary changes identifiable with LUS in dengue patients admitted to the Hospital for Tropical Diseases in Mahidol University, Bangkok, and the Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand. The LUS findings were described according to standard criteria, including the presence of A, B1, B2, and C patterns in eight chest regions and the presence of pleural effusions. From November 2017 to April 2018, 50 patients with dengue were included in the study. LUS was performed during the febrile phase for nine patients (18%) and during the critical-convalescence phase for 41 patients (82%). A total of 33 patients (66%) had at least one abnormality discovered using LUS. Abnormal LUS findings were observed more frequently during the critical-convalescence phase (N = 30/41; 73%) than during the febrile phase (N = 3/9; 33%) (P = 0.047). Abnormal aeration patterns were observed in 31 patients (62%). Only B patterns with only multiple B lines were observed in 21 patients (42%); of these patients, three had already exhibited B patterns during the febrile phase (N = 3). C patterns (N = 10; 24%), pleural effusion (N = 10; 24%), and subpleural abnormalities (N = 11; 27%) were observed only during the critical-convalescence phase. LUS can detect signs of capillary leakage, including interstitial edema and pleural effusions, early during the course of dengue.

Safety and Immunogenicity of an Inactivated Recombinant Newcastle Disease Virus Vaccine Expressing SARS-CoV-2 Spike: Interim Results of a Randomised, Placebo-Controlled, Phase 1/2 Trial.

BACKGROUND: Production of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and middle-income countries is needed. NDV-HXP-S is an inactivated egg-based Newcastle disease virus vaccine expressing the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It's being developed in Thailand, Vietnam, and Brazil; herein are initial results from Thailand. METHODS: This phase 1 stage of a randomised, dose-escalation, observer-blind, placebo-controlled, phase 1/2 trial was conducted at the Vaccine Trial Centre, Mahidol University (Bangkok). Healthy adults aged 18-59 years, non-pregnant and negative for SARS-CoV-2 antibodies were eligible. Participants were block randomised to receive one of six treatments by intramuscular injection twice, 28 days apart: 1 µg±CpG1018 (a toll-like receptor 9 agonist), 3 µg±CpG1018, 10 µg, or placebo. Participants and personnel assessing outcomes were masked to treatment. The primary outcomes were solicited and spontaneously reported adverse events (AEs) during 7 and 28 days after each vaccination, respectively. Secondary outcomes were immunogenicity measures (anti-S IgG and pseudotyped virus neutralisation). An interim analysis assessed safety at day 57 in treatment-exposed individuals and immunogenicity through day 43 per protocol. ClinicalTrials.gov ( NCT04764422 ). FINDINGS: Between March 20 and April 23, 2021, 377 individuals were screened and 210 were enrolled (35 per group); all received dose one; five missed dose two. The most common solicited AEs among vaccinees, all predominantly mild, were injection site pain (<63%), fatigue (<35%), headache (<32%), and myalgia (<32%). The proportion reporting a vaccine-related AE ranged from 5·7% to 17·1% among vaccine groups and was 2·9% in controls; there was no vaccine-related serious adverse event. The 10 µg formulation's immunogenicity ranked best, followed by 3 µg+CpG1018, 3 µg, 1 µg+CpG1018, and 1 µg formulations. On day 43, the geometric mean concentrations of 50% neutralising antibody ranged from 122·23 IU/mL (1 µg, 95% CI 86·40-172·91) to 474·35 IU/mL (10 µg, 95% CI 320·90-701·19), with 93·9% to 100% of vaccine groups attaining a ≥4-fold increase over baseline. INTERPRETATION: NDV-HXP-S had an acceptable safety profile and potent immunogenicity. The 3 µg and 3 µg+CpG1018 formulations advanced to phase 2. FUNDING: National Vaccine Institute (Thailand), National Research Council (Thailand), Bill & Melinda Gates Foundation, National Institutes of Health (USA).

The -11377C > G adiponectin gene polymorphism alters the adiponectin concentration and the susceptibility to type 2 diabetes in Thais.

The aims of this study were first to detect the levels of adiponectin, insulin, albumin, glucose, alanine aminotransferase (ALT), lipids, homeostasis model assessment for insulin resistance (HOMA-IR), and anthropometric variables in type 2 diabetes mellitus (T2DM) as well as healthy control groups, and to determine whether two adiponectin gene polymorphisms, at the position -11377C > G as well as +45T > G, are associated with serum levels of adiponectin and other variables; then to search for the association between these two single nucleotide polymorphisms (SNPs) of the adiponectin gene and T2DM. We investigated 93 T2DM patients and 90 healthy volunteers. Compared with the healthy control group, the T2DM group had significantly lower adiponectin levels. Waist circumference, total cholesterol, ALT, glucose, insulin, and HOMA-IR scores were significantly higher in the T2DM group than in the control group. The polymorphism of the adiponectin gene at position -11377C > G among type 2 diabetes subjects showed that the adiponectin concentration was significantly lower in CG/GG genotypes (6.2 µg/mL) than the CC genotype (7.8 µg/mL), whereas SNP +45T > G was not associated with adiponectin levels. Adiponectin gene polymorphisms at position -11377C > G and +45T > G were significantly more frequent in type 2 diabetes patients than in the control group (p = 0.022; p = 0.045, respectively). However, multivariate logistic regression analysis showed that the strong impact on T2DM was found for -11377C > G gene polymorphism (p = 0.023) and waist circumference (p < 0.001). Therefore, the single nucleotide polymorphism of -11377C > G in adiponectin promoter region has impact on the lower adiponectin concentrations, and may influence susceptibility to T2DM in Thais.

Cytokine Expression in Dengue Fever and Dengue Hemorrhagic Fever Patients with Bleeding and Severe Hepatitis.

Dengue is the most common mosquito-borne flaviviral infection in the world today. Several factors contribute and act synergistically to cause severe infection. One of these is dysregulated host immunological mediators that cause transient pathophysiology during infection. These mediators act on the endothelium to increase vascular permeability, which leads to plasma leakage compromising hemodynamics and coagulopathy. We conducted a prospective study to explore the expression of pro- and anti-inflammatory cytokines and how they relate to clinical dengue manifestations, by assessing their dynamics through acute dengue infection in adults admitted to the Hospital for Tropical Diseases, Bangkok, Thailand. We performed cytokine analysis at three phases of infection for 96 hospitalized adults together with serotyping of confirmed dengue infection during the outbreaks of 2015 and 2016. The serum concentrations of seven cytokines (interleukin [IL]-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha, and interferon gamma) were measured in duplicate using a commercial kit (Bio-Plex Human Cytokine Assay). In this study, the cytokine profile was suggestive of a T-helper 2 response. Most patients had secondary infection, and the levels of viremia were higher in patients with plasma leakage than those without plasma leakage. In addition, we observed that bleeding and hepatitis were associated with significantly higher levels of IL-8 during the early phases of infection. Furthermore, IL-6 levels in the early phase of infection were also elevated in bleeding patients with plasma leakage. These results suggest that IL-6 and IL-8 may act in synergy to cause bleeding in patients with plasma leakage.

Late boosting of the RV144 regimen with AIDSVAX B/E and ALVAC-HIV in HIV-uninfected Thai volunteers: a double-blind, randomised controlled trial.

BACKGROUND: The RV144 phase 3 vaccine trial in Thailand demonstrated that ALVAC-HIV (vCP1521) and AIDSVAX B/E administration over 6 months resulted in a 31% efficacy in preventing HIV acquisition. In this trial, we assessed the immunological effect of an additional vaccine boost to the RV144 regimen at varying intervals between the priming vaccine series and the boost. METHODS: RV306 is a double-blind, placebo-controlled, randomised clinical trial done at three clinical sites in Thailand. Eligible volunteers were HIV-uninfected individuals aged 20-40 years who were at low risk for HIV infection and in good health. A randomisation schedule was centrally generated with fixed sized strata for Research Institute for Health Sciences Chiang Mai and combined Bangkok clinics. Participants were randomly assigned to one of five groups and then further randomly assigned to either vaccine or placebo. All participants received the primary RV144 vaccine series at months 0, 1, 3, and 6. Group 1 received no additional boost, group 2 received additional AIDSVAX B/E and ALVAC-HIV (vCP1521) or placebo at month 12, group 3 received AIDSVAX B/E alone or placebo at month 12, group 4a received AIDSVAX B/E and ALVAC-HIV or placebo at month 15, and group 4b received AIDSVAX B/E and ALVAC-HIV or placebo at month 18. Primary outcomes were safety and tolerability of these vaccination regimens and cellular and humoral immune responses compared between the RV144 series alone and regimens with late boosts at different timepoints. Safety and tolerability outcomes were assessed by evaluating local and systemic reactogenicity and adverse events in all participants. This trial is registered at ClinicalTrials.gov (NCT01931358); clinical follow-up is now complete. FINDINGS: Between Oct 28, 2013, and April 29, 2014, 367 participants were enrolled, of whom 27 were assigned active vaccination in group 1, 102 in group 2, 101 in group 3, 52 in group 4a, 51 in group 4b, and 34 combined placebo across all the groups. No vaccine-related serious adverse events were recorded. Occurrence and severity of local and systemic reactogenicity were similar across active groups. Groups with late boosts (groups 2, 3, 4a, and 4b) had increased peak plasma IgG-binding antibody levels against gp70 V1V2 relative to group 1 vaccine recipients with no late boost (gp70 V1V2 92TH023 adjusted p<0·02 for each; gp70 V1V2 CaseA2 adjusted p<0·0001 for each). Boosting at month 12 (groups 2 and 3) did not increase gp120 responses compared with the peak responses after the RV144 priming regimen at month 6; however, boosting at month 15 (group 4a) improved responses to gp120 A244gD- D11 (p=0·0003), and boosting at month 18 (group 4b) improved responses to both gp120 A244gD- D11 (p<0·0001) and gp120 MNgD- D11 (p=0·0016). Plasma IgG responses were significantly lower among vaccine recipients boosted at month 12 (pooled groups 2 + 3) than at month 15 (group 4a; adjusted p<0·0001 for each, except for gp70 V1V2 CaseA2, p=0·0142) and at month 18 (group 4b; all adjusted p<0·001). Boosting at month 18 versus month 15 resulted in a significantly higher plasma IgG response to gp120 antigens (all adjusted p<0·01) but not gp70 V1V2 antigens. CD4 functionality and polyfunctionality scores after stimulation with HIV-1 Env peptides (92TH023) increased with delayed boosting. Groups with late boosts had increased functionality and polyfunctionality scores relative to vaccine recipients with no late boost (all adjusted p<0·05, except for the polyfunctionality score in group 1 vs group 4b, p<0·01). INTERPRETATION: Taken together, these results suggest that additional boosting of the RV144 regimen with longer intervals between the primary vaccination series and late boost improved immune responses and might improve the efficacy of preventing HIV acquisition. FUNDING: US National Institute of Allergy and Infectious Diseases and US Department of the Army.

Serum leptin levels and body composition in obese Thai children.

This study aimed to investigate the relationship between serum leptin concentrations and body composition among a sample of obese Thai children. A cross-sectional study was conducted in 158 schoolchildren, of whom 107 were obese and 51 normal weight; their mean age was 8.2 years. Body weight, height, waist circumference (WC), and subcutaneous skinfold thickness at 4 sites (triceps, biceps, subscapular, and supra-iliac) were measured. Total body fat (TBF) was determined by bioelectrical impedance analysis. Fasting blood samples were obtained to determine serum lipid profiles. The food intake of the children was estimated from interviews with the children and their mothers to elicit 24-hour food recall over 2 days. The results reveal subcutaneous fat skinfold, total body fat and waist circumference were significantly higher in obese than normal weight children (p < 0.001). Serum leptin levels and lipid profile results, ie serum triglycerides (TG), serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and energy intake, were also significantly higher in the obese children than their normal-weight peers. Stepwise multiple regression analysis indicates that among boys, WC (p < 0.001) and serum TG (p = 0.019), and among girls, WC (p < 0.001) and TBF (p = 0.030), were significantly associated with leptin concentrations. No associations were found between leptin and energy intake in these children. A prospective study should investigate the influence of leptin levels on weight gain and subcutaneous adiposity, and the interrelationship between food intake and circulating leptin levels in children.